1. Field of the Invention
The present invention relates to an improved method for magnetic resonance spectroscopy or imaging and, more specifically, it relates to a method for determining longitudinal spin relaxation time or imaging longitudinal spin relaxation time or producing images which substantially reflect longitudinal spin relaxation time contrast and, most specifically, it is particularly advantageous in determining changes in the longitudinal spin relaxation times in a patient. The invention also relates to an improved magnetic resonance spectroscopy or imaging apparatus and, more specifically, it relates to such an apparatus for determining longitudinal spin relaxation time or imaging longitudinal spin relaxation time or producing images which substantially reflect longitudinal spin relaxation time contrast.
2. Description of the Prior Art
The determination of spin-lattice relaxation times is a useful procedure in the fields of both high-resolution Magnetic Resonance (MR) spectroscopy and in Magnetic Resonance Imaging (MRI). In these procedures, a specimen is placed in a magnetic field causing resonating nuclei of the specimen, or "nuclear spins", to generate longitudinal spin magnetization. In a common procedure, this magnetization is inverted by the application of a radio frequency (RF) pulse to the specimen capable of nutating the longitudinal spin magnetization by 180.degree.. When the magnetization of the specimen's nuclear spins is inverted, it spontaneously returns to the non-inverted equilibrium state. The return to the equilibrium state occurs in substantially exponential fashion having a time constant which is characteristic of the molecular environment of the nuclear spin. This time constant is conventionally given the name longitudinal spin relaxation time, T.sub.1.
During the return to the equilibrium (or fully relaxed) state, the longitudinal magnetization cannot be directly detected. The instantaneous amount of longitudinal magnetization can be measured, however, by applying a sampling RF pulse. This sampling RF pulse nutates the longitudinal magnetization into the transverse plane, thereby creating transverse spin magnetization. Maximum transverse spin magnetization following inversion is generated by the application of a 90.degree. nutation. Unlike longitudinal magnetization, transverse spin magnetization is capable of inducing a signal in a receiver coil placed near the specimen.
The signal induced in the receiver coil carries significant information about the local environment of signal generating nuclei. If the signal is acquired in a homogeneous magnetic field, then the spectral components of the signal can be resolved to provide a MR spectrum in which different peaks arise from populations of nuclei in different molecules (or parts of a molecule). The T.sub.1 of individual peaks can vary considerably across a spectrum and can provide useful analytical information about molecular structure.
If the spatial distribution of transverse spin magnetization is to be measured (as in MRI), then the phase of the transverse spin magnetization can be varied as a function of position using magnetic field gradient pulses of selected intensities and durations. This gradient-induced phase variation encodes the location of the induced spin magnetization within the magnetic field. Two or three-dimensional images of the distribution of spin magnetization can be generated by repeating the sequence of RF and magnetic field gradient pulses with a series of different gradient intensities, acquiring the MR signals thereby generated, and applying the appropriate mathematical reconstruction techniques such as multi-dimensional Fourier Transform (FT) or back-projection algorithms, or the like.
Determination of T.sub.1 with previously available methods in MR spectroscopy and MRI typically requires a long sequence time. This is because the longitudinal magnetization must be measured at multiple points in time after the inversion pulse to accurately determine the time-constant of the recovery, and because only a single sampling pulse can be used during each recovery process. This is because the application of a sampling pulse disturbs the longitudinal spin magnetization and, hence, compromises the integrity of measurements generated by any subsequent sampling pulses. Therefore, best results are obtained when full recovery of longitudinal spin magnetization occurs after each sampling pulse.
For in vivo applications, the time for full relaxation is typically between 1 and 5 s, since most in vivo T.sub.1 values are between 300 and 1500 ms. Determination of T.sub.1 for each pixel in an image could require examination times as long as an hour or more, since enough data must be acquired to construct an image or set of images (e.g., with a resolution of 256.times.256), for each of several sampling times (e.g., 4-8) after each inversion pulse.
T.sub.1 is a fundamental MR parameter which characterizes the time taken for nuclear spins to align with the main magnetic field. The value of T.sub.1 depends critically on the amount of molecular level motion present at the MR frequency, and is a key determinant of contrast in MR images. See, generally, Bottomley, P. A. et al., "A review of normal tissue hydrogen NMR relaxation times and relaxation mechanisms from 1-100 MHz: Dependence on tissue type, NMR frequency, temperature, species, excision, and age," Med. Phys. 1984, Vol. 11, pp. 425-48; and Bottomley, P. A. et al., "A review of .sup.1 H nuclear magnetic resonance relaxation in pathology: Are T.sub.1 and T.sub.2 u diagnostic?" Med. Phys. 1987, Vol. 14, pp. 1-37.
While MR image intensity is dependent on T.sub.1, T.sub.1 images (i.e., images whose intensity is directly proportional to T.sub.1) are rarely used in medical MR because conventional methods of T.sub.1 imaging are too time-consuming, and because of the poor specificity of T.sub.1 as a diagnostic indicator, which makes them no more useful than images whose signal is proportional to the MR signal.
A conventional method of measuring T.sub.1 is to apply an RF inversion (180.degree.) pulse followed by a delay period, T.sub.1, and then to apply a read-out (90.degree.) RF pulse. See Vold, R. L. et al., J. Chem. Phys. 1968, Vol. 48, p. 3831.
This sequence is repeated at intervals T.sub.R &gt;&gt;T.sub.1 for a series of different T.sub.1 values. The resultant signals are fitted to an exponential whose time constant is 1/T.sub.1. When applied to MR imaging, the read-out pulse is replaced by an MR imaging sequence. See Edelstein, W. A. et al., J. Phys. Med. Biol. 1980, Vol. 25, pp. 51-56.
Hence, multiple images must be acquired for many different T.sub.1 values and a T.sub.1 image can only be constructed after fitting an exponential to the MR signals in each picture element (i.e., pixel) of the image, determining the time-constants, and displaying them proportional to image intensity. This method is extremely time-consuming because of the delay caused by the T.sub.R &gt;&gt;T.sub.1 condition, which applies to acquisition of each "frame" of an image, and which is generally impractical for medical applications. Nevertheless, acquisition of an image preceded by an inversion pulse at T.sub.1 remains a useful method of enhancing contrast due to differences in T.sub.1. See Young, I. R. et al., "Initial Clinical Evaluation of a Whole Body Nuclear Magnetic Resonance (NMR) Tomograph," J. Comp. Assist. Tomogr. 1982, Vol. 6, pp. 1-18.
U.S. Pat. No. 5,387,866 discloses the inversion recovery method of measuring T.sub.1, involving application of a 180.degree. inversion pulse followed by detection or read-out pulses that are selective for different slices in a specimen. The detection pulses are offset in frequency to select different regions in the specimen, and the flip-angles of the pulses are the same.
U.S. Pat. No. 5,363,042 similarly discloses the use of the inversion recovery sequence and employs gradient pulses to measure T.sub.1 in conjunction with blood flow measurements.
U.S. Pat. No. 4,733,186 discloses the inversion recovery method generally including an inversion pulse and plural RF read-out pulses in the range 5.degree.-20.degree. to slightly change the longitudinal magnetization. The RF read-out pulses all have the same flip-angle.
T.sub.1 can also be measured by the partial saturation sequence wherein RF pulses (e.g., 90.degree. pulses) are applied at period T.sub.R .ltoreq.T.sub.1 until the MR signal reaches a steady-state value. See Freeman, R. et al., J. Chem. Phys. 1971, Vol. 54, p. 3367. T.sub.1 is calculated by fitting the MR signal strengths measured for a number of different T.sub.R values to an exponential with time-constant T.sub.R /T.sub.1. Again, this is rarely used for imaging T.sub.1 because it requires image acquisitions to be repeated for many (e.g., &gt;2) T.sub.R values with steady-state equilibrium being established prior to commencement of each acquisition. The method is used, however, for providing T.sub.1 -dependent image contrast with a carefully selected T.sub.R value.
Sequences of alternating 90.degree. and 180.degree. pulses applied with T.sub.R &lt;5T.sub.1 can also be used to provide T.sub.1 contrast in images, and to measure T.sub.1 in shorter scan times than in the inversion recovery method. In this case, T.sub.1 is calculated from the two signals, S1 and S2, in a "SUFIR" sequence: "90.degree.-t-180.degree.-t-90.degree.(acquire S1)-t-180.degree.-t-90.degree.(acquire S2)." Time t is set between 0.5T.sub.1 and 3T.sub.1, but the spacing between applications of the complete sequences, for averaging (or imaging) purposes, for example, must allow for complete relaxation. While a T.sub.1 measurement is theoretically possible from a single "SUFIR" sequence application, images of T.sub.1 would take much longer if S1 and S2 correspond to each frame of an image, requiring repeated applications to build an entire MR image. See, generally, Edelstein, W. A. et al., JCAT 1983, Vol. 7, pp. 391-401; and Canet, D. et al., "Superfast T.sub.1 Determination by Inversion-Recovery," J. Magn. Reson. 1988, Vol. 77, pp. 483-90.
In addition, the "SUFIR" sequence does not yield optimum efficiency since MR signals are acquired for every five pulses that are applied and because the two 180.degree. pulses generate no MR signals.
Another approach is the dual angle method which is comprised of two sequences of pulses of flip-angles &lt;90.degree. (e.g., 15.degree., 60.degree.) applied with a constant period T.sub.R .ltoreq.T.sub.1. See Bottomley, P. A. et al., "The Dual-Angle Method for Fast, Sensitive T.sub.1 Measurement in Vivo with Low-Angle Adiabatic Pulses," J. Magn. Reson. B. 1994, Vol. 104, pp. 159-67. A series of first (e.g., 15.degree.) pulses are applied until steady-state equilibrium is established, then MR signals are acquired following every pulse. Next, a series of second pulses (e.g., 60.degree.) are applied and signals again are acquired at steady-state. T.sub.1 is calculated from the ratio of the two signals. Unlike the SUFIR method, the dual angle method is more efficient when much signal averaging or imaging is required since the extra data can be acquired simply by adding acquisitions once steady-state conditions are established. However, the method still requires two separate acquisition sequences, and two establishments of steady-state equilibrium.
The dual angle method takes advantage of low-angle adiabatic "BIRP" pulses which can be set highly accurately without the need for lengthy pulse calibration procedures. The flip-angles can be dialed up and are correctly set to within about .+-.1.degree. over a wide range of transmitter power levels and MR RF field inhomogeneity. See Bottomley, P. A. et al., "BIRP, an Improved Implementation of Low-Angle Adiabatic (BIR-4) Excitation Pulses," J. Magn. Reson. A. 1993, Vol. 103, pp. 242-44.
U.S. Pat. No. 5,347,218 discloses spin-echo MRI in a conventional manner, with short sequence repetition times, in which an approximately 90.degree. RF pulse is followed by a substantially 180.degree. RF pulse to detect a spin-echo at time 2.tau..
U.S. Pat. Nos. 5,202,632 and 5,239,266 disclose an MRI sequence for producing images with improved T.sub.1 contrast or T.sub.2 (i.e., transverse relaxation time) contrast. A .theta..degree. (e.g., 90.degree.) excitation pulse is followed by one or more 180.degree. refocusing pulses. To enhance contrast and the signal-to-noise ratio of relatively long T.sub.1 tissues for relatively low spatial frequency encoded sub-sequences, the initial angle .theta. is reduced for the lower spatial frequencies.
U.S. Pat. Nos. 5,281,913 and 5,307,015 disclose an apparatus and methods of measuring T.sub.1 at different magnetic field strengths by soaking a specimen in a different magnetic field followed by a T.sub.1 measurement in the main magnetic field of an MR system.
In U.S. Pat. No. 5,281,913, T.sub.1 is measured by repeating two MR spin echo sequences with two different T.sub.R values. A 90.degree. pulse may be applied prior to switching the magnetic field.
In U.S. Pat. No. 5,307,015, a pulse of flip-angle .alpha..degree. is applied, the magnetic field is switched to a new value for some time .tau. and, then, is switched back to the main magnetic field, after which the MRI experiment is completed. This is repeated for a plurality of .alpha. values. To speed up the process, a short T.sub.R is employed and the steady-state, incompletely relaxed, magnetization is measured in a separate experiment. For each T.sub.1 relaxation measurement, at least three MRI sequences are applied.
U.S. Pat. No. 5,245,282 discloses a T.sub.1 contrast enhancing sequence involving the use of a single T.sub.1 preparation pulse, such as a .ltoreq.180.degree. pulse, followed by a delay period, and application of a conventional gradient echo or other imaging sequence. A 180.degree. inversion pulse is followed by a sequence of 128 10.degree. pulses. In U.S. Pat. No. 5,245,282, it is disclosed to vary the flip-angle as a function of a phase-encoding step and is claimed to provide variable flip-angles in conjunction with a pulse sequence comprised of a magnetization preparation period, a data acquisition period, a magnetization recovery period to allow relaxation before application of the next cycle, and repetition of these steps to cover the image k-space.
U.S. Pat. No. 5,311,133 discloses a pulse sequence for performing rapid MRI with sequence spacing T.sub.R &lt;T.sub.2, the transverse relaxation time. The RF excitation pulses applied in this sequence have the same flip-angle which is preferably less than 20.degree..
A deficiency in known methods for determining T.sub.1 is the requirement to establish equilibrium or steady-state conditions on multiple occasions. For imaging acquisitions, they require multiple sequence applications. This makes them unsuitable for determining T.sub.1 changes in dynamic functional MR studies, such as in the heart or in the brain, and for minimally invasive MR therapy studies, for example, employing hyper/hypothermy in cancerous tissue. See, generally, Edelman, R. R. et al., Radiol. 1994, Vol. 190, pp. 771-77; Manning, W. J. et al., "First-Pass Nuclear Magnetic Resonance Imaging Studies Using Gadolinium-DTPA in Patients With Coronary Artery Disease," J. Am. Coll. Cardiol. 1991, Vol. 18, pp. 959-65; and Kwong, K. K. et al., "Dynamic magnetic resonance imaging of human brain activity during ring primary sensory stimulation," Proc. Natl. Acad. Sci. USA 1992, Vol. 89, pp. 5675-79.
As T.sub.1 changes are believed to be the prime mechanism for the changing contrast responsible for the functional changes which are manifest as changes in image contrast, further improvements to expedite the acquisition of T.sub.1 information are extremely desirable.
For these reasons, there remains a very real and substantial need for an improved apparatus and method of operation thereof for determining or imaging longitudinal spin relaxation time or producing images which substantially reflect longitudinal spin relaxation time contrast.